Bone strength, or the ability to resist fractures, is critically dependent on bone health in young and middle years - the higher the peak bone mass achieved in younger years, the lower the likelihood of developing osteoporosis in later life. We postulate that social and psychological factors over the lifespan affect bone strength by influencing the level of peak strength achieved in young adulthood, the maintenance of bone strength through middle adulthood, and the rate of decline in older ages. Our specific aims are to: Aim 1. Determine the strength of the association between long-term psychosocial profiles and bone strength. Aim 2. Determine the strength of the association between biological system dysregulation and bone strength. Aim 3. Determine the extent to which the putative biological pathways mediate the associations between long- term psychosocial profiles and bone strength. The project will draw on three cohort studies (Midlife in the United States, the Wisconsin Study of Late Life Resilience, and the MacArthur Study of Successful Aging) that together, have data from adults, ages 24 and up, and have 9 or more years of follow up. This project is uniquely optimized to explore this thesis because: 1) In addition to using standard bone mineral density assessments, we will expand bone health outcomes to include comprehensive assessments of bone strength and bone metabolic balance. 2) We will determine the influence not only of social adversity and psychological ill-health but also of social advantage and psychological well-being on bone outcomes. 3) A lifespan perspective will be adopted, wherein long-term psychosocial influences will be used as predictors of adult bone strength. This project will be the first comprehensive attempt to delineate the influences of multiple psychosocial domains over the life course (including early life experiences) on bone strength, and to identify the biological pathways through which these influences are exerted. Its strengths lie in the unmatched breadth, depth, and longitudinal aspect of psychosocial and biological assessments in the 3 cohort studies, the complementary breadth and depth of bone outcomes assessed across the 3 studies, the lengths of follow up, the large range of ages spanned, and the novel approach to the research questions: the adoption of the more appropriate life- history approach to estimating psychosocial influences on bone strength, the equal consideration given to psychosocial advantage and adversity, and the innovative and comprehensive assessment of bone strength, that goes beyond the usual bone density metric of strength. PUBLIC HEALTH RELEVANCE: This project will determine how bone strength (i.e., bone's ability to resist fracture) is affected by life histories of socioeconomic status (financial condition and social status), social relationships (with parents, spouse, friends, children, etc.), and psychological health (both positive aspects such as happiness, life satisfaction, personal growth and purpose in life, and negative ones, such as depression and anxiety). We will also examine which biological changes might explain these social and psychological effects on bone health. Discovery of these effects on bone strength and the biological mechanisms will mean that we can identify and target those at high risk for fractures for early screening and interventions, with the eventual goal of reducing the burden of osteoporosis (low bone strength) on quality of life and mortality.